The goals of the clinical project are: to continue and expand present therapeutic studies for patients with malignant gliomas; to design, implement and analyze new Phase I/II trials conducted at UAB as institutional or cooperative protocols; and to maintain an active multidisciplinary neuro-oncology group to facilitate the transfer of laboratory observations into treatment protocols for patients. Specific Aim No.1 is to expand our experience with intra-arterial (IA) cisplatin through two concurrent Phase II protocols, one for patients with recurrent tumors and one for patients with newly diagnosed tumors who will receive intensified IA cisplatin prior to radiotherapy. Both studies will feature selective infusion of cisplatin into major intracellular arteries. Specific Aim No.2 is to explore the safety and efficacy of intensified systemic chemotherapy for malignant gliomas, including the administration of high-dose chemotherapy combined with hematopoietic growth factors and/or autologous bone marrow transplantation. The initial study to be carried out is a Phase I trial of continuous high-dose intravenous (IV) infusion of hydroxyurea with escalating treatment duration for patients with recurrent malignant gliomas. Specific Aim No.3 is to study the safety and efficacy of monoclonal antibody (MAb) 425, a murine IgG which binds to the epidermal growth factor receptor. Three sequential protocols will be carried out, including a Phase I dose escalation study of IV unmodified MAb 425 for recurrent tumors, and then a Phase II study of the antitumor efficacy of radiolabeled MAb 425 given to patients with newly diagnosed malignant gliomas prior to radiotherapy or chemotherapy. Specific Aim No.4 will be to design and conduct Phase I and Phase II trials of biologic response modifiers, including interferon and TNFalpha, based on the results of current clinical studies and of Projects No 1-5 in this proposal. Concurrent with these treatment protocols, Specific Aim No. 5 is to study the utility of thallium-201 SPECT imaging for malignant gliomas, both in the practical clinical management of patients and in studying correlations between tumor cell uptake of thallium-201 and expression of a number of proteins being studied in other Projects, particularly TNFalpha, TGFbeta, myosin II, vitronectin, and the integrins.